The present invention relates to the sealing and dispensing of pharmaceuticals and, more particularly to the sealing and dispensing of a lyophilized drug in a cartridge assembly.
In current technology, drugs or compounds manufactured for various injections are generally encapsulated in sterile glass cartridges. The glass cartridges characteristically have a sealed end with the other end of the cartridge generally having a restricted opening in the form of a neck having a circumferential flange. The opening can be closed off with a rubber membrane held into place with an aluminum seal crimped therearound. Where the drug or compound is to be later dispensed either directly from the cartridge or in a dispensing device such as a pen dispenser, the cartridge includes at the end opposite the restricted opening, an open end generally having a rubber plunger closing the open end. The rubber plunger also acts as a piston to force the drug or compound contained within the cartridge out of the restricted opening into which there has generally been inserted a cannula, by action of a plunger rod exerting axial pressure upon the rubber plunger.
Cartridges for use with dispenser devices or pens as described above are generally known in the prior art. U.S. Pat. No. 4,936,833 Sams, shows a typical glass cartridge having an open end with a plunger therein, and an opposite end including a restricted opening sealed with a rubber membrane and crimped metal collar. The cartridge is insertable into a housing forming a part of a dispenser pen, with a cap for receiving a two ended cannula. Typical of these device are U.S. Pat. No. 4,883,472 Michel, and U.S. Pat. No. 4,973,318 Holm et al.
Lyophilized drugs or compounds are currently being utilized as the basis for injectionable compounds, such as human growth hormone (HGH), insulin, and the like. Lyophilization is the rapid freezing of a material at a very low temperature followed by rapid dehydration by sublimination in a high vacuum. The lyophilized compound is generally contained in a glass vial or cartridge. However, the process described above is not suitable for lyophilized compounds which are moisture and oxygen sensitive. When the moisture is removed from the compound during lyophilization, the oxygen in the glass cartridge containing a lyophilized drug must be replaced with nitrogen after the lyophilization process. This step of replacing the oxygen with nitrogen is termed nitrogen overlay and is accomplished within the lyophilizing chamber (freeze dryer).
One technique is to lyophilize the drugs or compounds in rubber stoppered glass vials. During lyophilization of the compounds in the glass vials, the rubber stopper used to close the vial is partially seated in the neck of the vial. The moisture which is removed from the compound during lyophilization is vented out through grooves or slots formed in the rubber stopper. As a general method of closing the vials, the shelves of the lyophilization chamber vertically move together to press the rubber stopper down into the vial, until the vents in the stopper are well inside the neck opening of the vial. An aluminum seal is then crimped about a flange on the neck of the vial.
The use of aluminum as a crimping seal for the rubber stopper is not, however, preferred due to the possibility of aluminum dust or particles contaminating the compound during the initial crimping, reconstitution, or administration processes. In addition, such processes as above are not well suited for efficient lyophilization.
Thus, it is desired to eliminate the aluminum crimping seal as well as provide an easier method of assuredly allowing lyophilization of a compound and sealing the same.
In order to administer a lyophilized compound, it is necessary to reconstitute the compound prior to administration with a suitable diluent. Reconstitution is accomplished by using a syringe with a needle to withdraw the diluent from a separate vial and inject it into the vial containing the lyophilized compound. The vial containing the lyophilized compound is placed in a holder during reconstitution. Because the cartridge is filled with the lyophilized compound and nitrogen, addition of the diluent produces extra pressure within the cartridge which creates the possibility of forcing the plunger out of the cartridge. Having the plunger forced out of the cartridge during reconstitution would undesirably result in a total loss of the compound.
During reconstitution, the diluent injected from the syringe into the cartridge directly impinges upon the lyophilized compound which causes the lyophilized compound to foam. The foam undesirably creates extra head space within the cartridge such that the proper amount of diluent is not mixed with the compound, resulting in an improper diluent to compound ratio. In order to alleviate this, one must wait for the foam to subside.
A patient needle is then attached to the disc sealed end of the cartridge which thus allows the compound to be injected. Current injector pens dispense a selectable amount of drug depending on the required dosage. A plunger mechanism, including a plunger rod, pushes against the plunger in the cartridge. After each injection, the plunger mechanism and plunger rod retract during a resetting function of the injector pen. However, complete disengagement of the plunger rod from the plunger mechanism during retraction is highly undesirable, and can render the injector pen inoperative.
Because of the expanding use of pen dispensers or injectors utilizing cartridges for the administration of injectionable compounds, it is desired to provide a lyophilized compound in an improved cartridge suitable for use in an injector pen.